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Response Rate (RR), defined as the proportion of subjects who have a ≥35% reduction from baseline in volume of spleen at the end of Cycle 6 as measured by Magnetic Resonance Imaging (MRI) (or CT scan in subjects with contraindications for MRI) [ Time Frame: 6 months ]

Proportion of subjects with a ≥50% reduction in length of spleen by palpation from baseline at the end of Cycle 6 [ Time Frame: 6 months ]

Response Rate at the end of Cycle 3, defined as the proportion of subjects who have a ≥35% reduction from baseline in volume of spleen at the end of Cycle 3 as measured by MRI (or CT scan in subjects with contraindications for MRI) [ Time Frame: 6 months ]

Percent change of spleen volume at the end of Cycles 3 and 6 from baseline as measured by MRI (or CT scan in subjects with contraindications for MRI) [ Time Frame: 6 months ]

Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03 [ Time Frame: approximately 5 years ]

Plasma concentrations of SAR302503 [ Time Frame: 4 months ]

The effect of SAR302503 on the JAK2V617F allele burden [ Time Frame: 2 years ]

Proportion of subjects with a ≥50% reduction in length of spleen by palpation from baseline at the end of Cycle 6 [ Time Frame: 6 months ]

Response Rate by Cycle 6 (RR6), defined as the proportion of subjects who have a ≥35% reduction from baseline in volume of spleen at any time up to Cycle 6 as measured by MRI (or CT scan in subjects with contraindications for MRI) [ Time Frame: 6 months ]

The effect of SAR302503 on the JAK2V617F allele burden [ Time Frame: 2 years ]

Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03 [ Time Frame: approximately 5 years ]

Plasma concentrations of SAR302503 [ Time Frame: 4 months ]

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib

Official Title ICMJE

A Phase II, Multicenter, Open Label, Single Arm Study of SAR302503 in Subjects Previously Treated With Ruxolitinib and With a Current Diagnosis of Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Brief Summary

Primary Objective:

- To evaluate the efficacy of once daily dose of SAR302503 in subjects previously treated with ruxolitinib and with a current diagnosis of intermediate-1 with symptoms, Intermediate-2 or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (Post-PV MF), or post-essential thrombocythemia myelofibrosis (Post-ET MF) based on the reduction of spleen volume at the end of 6 treatment cycles;

Secondary Objectives:

To evaluate the effect of SAR302503 on Myelofibrosis (MF) associated symptoms as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary

To evaluate the durability of splenic response

To evaluate the splenic response to SAR302503 by palpation at the end of Cycle 6

To evaluate the splenic response to SAR302503 at the end of Cycle 3

To evaluate the effect of SAR302503 on the Janus kinase 2 (JAK2) V617F allele burden

To evaluate the safety and tolerability of SAR302503 in this population

To evaluate plasma concentrations of SAR302503 for population PK analysis, if warranted

Detailed Description

The expected duration of the treatment in this study is approximately 8 months, based on a maximum 28-day screening period, followed by a 6-month (6-cycle) treatment period, and an EOT visit for subjects who will not continue the treatment after completing the 6 cycles of SAR302503, or discontinue the treatment early for any reasons as well as a follow-up visit which should occur 30 days after the last administration of SAR302503. Patients who continue to benefit clinically will be allowed to remain on study medication beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Completed

Actual Enrollment ICMJE (submitted: June 10, 2014)

97

Original Estimated Enrollment ICMJE (submitted: January 31, 2012)

41

Actual Study Completion Date

April 2014

Actual Primary Completion Date

April 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion criteria:

Diagnosis of PMF or Post-PV MF or Post-ET MF, according to the 2008 World Health Organization and IWG-MRT response criteria

Subjects who previously received Ruxolitinib treatment for PMF or Post-PV MF or Post-ET MF or PV or ET for at least 14 days (exposure of <14 days is allowed for subjects who discontinued Ruxolitinib due to intolerability or allergy) and discontinued the treatment for at least 14 days prior to the first dose of SAR302503

MF classified as Intermediate-1 with symptoms, Intermediate-2 or high-risk by Dynamic International Prognostic Scoring System (Passamonti et al., Blood 2010)

Spleen ≥5 cm below costal margin as measured by palpation

Male and female subjects ≥18 years of age

Signed written informed consent

Exclusion criteria:

Splenectomy

Eastern Cooperative Oncology Group (ECOG) performance status of >2 before the first dose of SAR302503 at Cycle 1 Day1

The following laboratory values within 14 days prior to the initiation of SAR302503:

Subjects with any other prior malignancies are not eligible, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which subject has been disease-free for at least 5 years

Any chemotherapy, immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), Anagrelide, immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin), or hormones (eg, androgens, danazol) within 14 days prior to initiation of SAR302503; darbepoetin use within 28 days prior to initiation of SAR302503.The only chemotherapy allowed will be hydroxyurea within 1 day prior to initiation of SAR302503